Insulin-like growth factors and their transfer protein in the blood of patients with primary and recurrent soft tissue sarcomas

Abstract

Introduction. Soft tissue sarcomas (STS) are rare diseases but their characteristic tendency for recurrence and high mortality dictate the need for the search for prognostic biomarkers for identification of patients with the risk of recurrence. In this context, the system of insulin-like growth factors (IGF) and their insulin-like growth factor-binding proteins (IGFBP) is of interest because it was shown that disruption of the IGF system regulation leads to cancer cell proliferation and migration and chemotherapy resistance.The study objective is to investigate the levels of the IGF system components in blood of patients with primary and recurrent STS.Materials and methods. In total, 54 patients with STS, T2bN0M0, were examined: 12 men and 12 women with primary STS, 10 men and 20 women with recurrent STS, as well as healthy donors (10 men and 10 women). Mean patient age was 63.1 ± 0.9 years. In blood sampled prior to treatment, the levels of insulin-like growth factor 1 (IGF1), insulin-like growth factor 2 (IGF2) and insulin-like growth factor-binding protein 2 (IGFBP2) were measured by ELISA using Mediagnost kits (Germany). Statistical analysis was performed using Statistica 10 software and non-parametric Mann-Whitney test.Results. In primary STS, the levels of IGF1 in men with G3–4 tumors and all women decreased 14- and 20-fold, respectively, compared to healthy donors. Additionally, an insignificant decrease of IGF2 level in men and a decrease of IGF1/IGF2 ratio by the factor of 8.8 in men with G3–4 tumors and by the factor of 24.3 in women were observed. In recurrences, IGF1 level decreased by 40 % in men and by 78–85.5 % in women, while IGF2 level in men with G3–4 tumors decreased by 19 %, in women increased by 21–58 % compared to donors. In women with primary STS and recurrences of G3–4 tumors, IGFBP2 was also elevated. In men with G3–4 tumors, changes in IGFBP2 levels were less significant and had an opposite trend compared to women.Conclusion. STS recurrence is accompanied by imbalance of IGF system components in blood, especially in patients of both sexes with G3–4 tumors. Correlation between increased IGFBP2 level in STS and clinical characteristics of the disease, especially in recurrence, suggest prognostic significance of this molecule.